Proteasome inhibitor bortezomib targeted tumor–endothelial cell interaction in T-cell leukemia/lymphoma
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Wen-Yu Shi & Li Wang & Dan Xiao & Yin Yao & Fan Yang & Xiao-Xing Jiang & Christophe Leboeuf & Anne Janin & Sai-Juan Chen &Wei-Li Zhao
- چاپ و سال / کشور: 2010
Description
Endothelial cells have special relevance in tumor progression. Here, we investigated the effect of the proteasome inhibitor bortezomib on tumor–endothelial cell interaction in T-cell leukemia/lymphoma. In vitro, Tleukemia/ lymphoma cell lines and primary T-leukemia/ lymphoma cells were cultured with endothelial cells, either together or separately in Millicell Hanging Cell Culture system, the latter permits mutual cell exchange. At clinically achievable concentrations, in addition to a direct cytotoxicity on T-leukemia/lymphoma cells, bortezomib inhibited tumor cell adhesion to endothelial cells and endothelial cell migration toward tumor cells. In vivo, a murine tumor xenograft model was achieved by subcutaneous injection of Jurkat cells. Bortezomib also triggered an inhibition on tumor–endothelial cell contact and subsequent tumor cell infiltration. Cell adhesion molecule intracellular cell adhesion molecule-1 expression was significantly downregulated both on the tumor cells and on the endothelial cells. Taken together, bortezomib could not only act on tumor cells themselves but also abrogate tumor cell interaction with endothelial cells. This delineates another therapeutic mechanism of bortezomib in T-cell malignancies.
Ann Hematol (2011) 90:53–58 DOI 10.1007/s00277-010-1022-1 Received: 26 March 2010 / Accepted: 21 June 2010 / Published online: 9 July 2010
